Lung cancer is one of the major causers of cancer-related deaths in the world. There are two primary types of lung cancers: small cell lung cancer and non-small cell lung cancer (NSCLC) (Carney, (1992a) Curr. Opin. Oncol. 4:292–8). Small cell lung cancer accounts for approximately 25% of lung cancer and spreads aggressively (Smyth et al. (1986) Q J Med. 61: 969–76; Carney, (1992b) Lancet 339: 843–6). Non-small cell lung cancer represents the majority (about 75%) of lung cancer and is further divided into three main subtypes: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (Ihde and Minna, (1991) Cancer 15: 105–54). In recent years, much progress has been made toward understanding the molecular and cellular biology of lung cancers. Many important contributions have been made by the identification of several key genetic factors associated with lung cancers. However, the treatments of lung cancers still mainly depend on surgery, chemotherapy, and radiotherapy. This is because the molecular mechanisms underlying the pathogenesis of lung cancers remain largely unclear.
A recent hypothesis suggested that lung cancer is caused by genetic mutations of at least 10 to 20 genes (Sethi, (1997) BMJ. 314: 652–655). Therefore, future strategies for the prevention and treatment of lung cancers will be focused on the elucidation of these genetic substrates, in particular, the genes localized on chromosome 11p15.5, a region shown to be associated with the development of lung cancer (Kondo et al. (1996) Oncogene 12:1365–8; O'Briant and Bepler, (1997) Genes Chromosomes Cancer 18:111–4; Sanchez-Cespedes et al. (1997) Clin Cancer Res 3:1229–35; Bepler et al. (1998) Cancer Detect Prev 22:14–9; Pitterle et al. (1999) Mamm Genome 10:916–22; Xu et al. (2001) Cancer Res 61:7943–9). A human PEN11B gene was mapped on this region (GenBank Accession No. AF020089), suggesting that PEN11B gene may have a role in the tumorigenic process of lung cancer. Therefore, the discovery of gene variants of PEN11B may be important targets for diagnostic markers of lung cancers.